Combikel Injectable Suspension

Indications

• Bacterial infections
• Pneumonia
• Meningitis
• Syphilis
• Rheumatic fever
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Dosing for children should be carefully determined based on weight and the specific condition being treated. Refer to the BNF for Children for precise dosing information.

Adults: Dosing varies based on the type and severity of infection. It is important to refer to clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Benzylpenicillin exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It does this by binding to penicillin-binding proteins (PBPs), which are essential for the cross-linking of peptidoglycan layers in bacterial cell walls. This inhibition leads to cell lysis and death, particularly in actively dividing bacteria.

Pharmacodynamics

The bactericidal activity of benzylpenicillin is time-dependent, meaning that its efficacy is related to the time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target organism. The drug is most effective against bacteria that are actively growing and dividing, as these are more dependent on cell wall synthesis.

Pharmacokinetics

Benzylpenicillin is poorly absorbed from the gastrointestinal tract, necessitating parenteral administration. Following intramuscular injection, peak plasma concentrations are typically reached within 30 to 60 minutes. The drug is widely distributed in body tissues and fluids, including the central nervous system, though it does not penetrate well into the eye and prostate. Benzylpenicillin is primarily eliminated via renal excretion, with a half-life of about 30 minutes to 1 hour in individuals with normal renal function. Renal impairment may prolong the half-life and necessitate dose adjustments.

Contra-indications

• Hypersensitivity to benzylpenicillin or other penicillins
• Previous severe allergic reactions to any beta-lactam antibiotics

Adverse effects

• Allergic reactions including anaphylaxis
• Skin rashes
• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Superinfection due to alteration of normal flora
• Neurotoxicity, particularly with high doses, potentially leading to seizures

Interactions

• Probenecid may increase the serum concentration of benzylpenicillin by inhibiting its renal excretion
• Benzylpenicillin may enhance the anticoagulant effect of warfarin
• Concurrent use with other nephrotoxic drugs may increase the risk of renal impairment

Precautions

• Use with caution in patients with renal impairment.
• Monitor for signs of anaphylaxis during the first dose.
• Caution in patients with a history of allergic reactions to multiple allergens.
• Consider risk of Clostridium difficile-associated diarrhea in prolonged therapy

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is not known to cause harm to the fetus. However, it should only be used if clearly needed.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, and is generally considered safe for use during breastfeeding, but caution is advised.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be stored in a refrigerator and used within a specified time frame as per the manufacturer's guidelines.

Formulations

• Injection - Benzylpenicillin sodium
• Injection - Benzylpenicillin procaine

Indications

• Tuberculosis
• Bacterial infections caused by susceptible strains of Mycobacteria
• Severe infections caused by Gram-negative bacteria

Dosage

Children: Refer to BNF for Children for appropriate pediatric dosing recommendations.

Adults: Refer to BNF for specific dosing guidance, as it may vary based on the indication and patient condition.

Mechanism of action

Dihydrostreptomycin binds to the 30S ribosomal subunit of bacteria, interfering with the initiation complex and causing misreading of the mRNA. This action leads to the production of nonfunctional proteins and ultimately results in bacterial cell death.

Pharmacodynamics

Dihydrostreptomycin exhibits concentration-dependent bactericidal activity against a variety of Gram-negative and some Gram-positive bacteria. Its efficacy is influenced by the peak concentration achieved relative to the minimum inhibitory concentration (MIC) of the organism.

Pharmacokinetics

Dihydrostreptomycin is administered parenterally due to poor oral absorption. It is widely distributed in body tissues and fluids, but does not penetrate well into the central nervous system. The drug is primarily eliminated by renal excretion, and its half-life can be prolonged in patients with renal impairment.

Contra-indications

• Hypersensitivity to dihydrostreptomycin or other aminoglycosides
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Ototoxicity, including hearing loss and vestibular dysfunction
• Nephrotoxicity, particularly with high doses or prolonged therapy
• Neuromuscular blockade
• Allergic reactions, including rash and anaphylaxis

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents such as vancomycin, amphotericin B, and non-steroidal anti-inflammatory drugs (NSAIDs)
• Potentially enhanced neuromuscular blockade with neuromuscular blockers

Precautions

• Use with caution in patients with pre-existing renal impairment
• Monitor renal function regularly during therapy
• Assess hearing function prior to and during treatment

Pregnancy

Dihydrostreptomycin is categorized as a category D drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dihydrostreptomycin is excreted in breast milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Injection solution